Spring 2016

FROM THE CHAIR

Dear Friends of BME at UCI,

As March madness is behind us and many sports teams are in the midst of spring training, the BME team at UCI is looking forward to the new season with rejuvenated anticipation. A successful sports team requires strong players through the draft and recruitment from free agency, and we as a department are determined to build a winning team. Starting from the “draft,” this year BME has a record number of both undergraduate and graduate applicants. On the faculty level, we heartily welcome Assistant Professor Tim Downing to the department. Downing joins us from the Broad Institute of Harvard, where he was a postdoctoral fellow in the Epigenomics Program. He received his doctorate from the UC Berkeley/UCSF Bioengineering Program, with a major in stem cells and tissue engineering and a minor in neuroengineering. He was also a football player during his undergraduate years at Northwestern University, so we are thrilled to get an athletic colleague to bolster our formidable faculty volleyball and basketball teams! In addition, we expect to have up to three new members joining our faculty ranks this fall. In terms of our current roster, we have a healthy distribution of junior to senior faculty (nine full, seven associate, seven assistant) and run four major research centers with annual budgets of more than $1M. Our junior colleagues have been outstanding, winning a high percentage of early career awards among their peers. Notably, BME assistant professors have won the NIH New Innovator’s Award five out of the last six years. This is akin to winning five out of six “Rookie of the Year” awards! In this newsletter, you also can read about Associate Professor Zoran Nenadic winning the Hiruma-Wagner Award from the Japanese Research Foundation, Professor Bruce Tromberg's election as an OSA Fellow, and Associate Professor Bernard Choi's election as an SPIE Fellow. I invite you to celebrate with us our many student achievements as well, as we join the whole BME community for our ultimate championship aspiration: “To Inspire Engineering Minds for the Advancement of Human Health!”

This newsletter is about the people we cherish at UCI BME, their stories, their aspirations, their visions and their accomplishments.

UCI Brain-Computer Interface Enables Paralyzed Man to Walk

Novel brain-computer interface technology created by UC Irvine researchers has allowed a paraplegic man to walk for a short distance.

In the preliminary proof-of-concept study, led by UCI biomedical engineer Zoran Nenadic and neurologist An Do, a person with complete paralysis in both legs due to spinal cord injury was able — for the first time — to take steps without relying on manually controlled robotic limbs.

The male participant, whose legs had been paralyzed for five years, walked along a 12-foot course using an electroencephalogram-based system that lets the brain bypass the spinal cord to send messages to the legs. It takes electrical signals from the subject’s brain, processes them through a computer algorithm, and fires them off to electrodes placed around the knees that trigger movement in the leg muscles.

“Even after years of paralysis, the brain can still generate robust brain waves that can be harnessed to enable basic walking,” said Nenadic, an associate professor of biomedical engineering. “We showed that you can restore intuitive, brain-controlled walking after a complete spinal cord injury. This noninvasive system for leg muscle stimulation is a promising method and is an advance of our current brain-controlled systems that use virtual reality or a robotic exoskeleton.”

Months of mental training to reactivate the brain’s walking ability and physical therapy were needed for the study participant to reach the stage where he could take steps. Wearing an EEG cap to read his brain waves, he was first asked to think about moving his legs. The brain waves this created were processed through a computer algorithm Nenadic had formulated to isolate those related to leg movement. The subject later was trained to control an avatar in a virtual reality environment, which validated the specific brain wave signals produced by the algorithm.

This training process yielded a custom-made system, Nenadic said, so that when the participant sought to initiate leg movement, the computer algorithm could process the brain waves into signals that could stimulate his leg muscles.

To make this work, the subject required extensive physical therapy to recondition and strengthen his leg muscles. Then, with the EEG cap on, he practiced walking while suspended 5 centimeters above the floor, so he could freely move his legs without having to support himself. Finally, he translated these skills to the ground, wearing a body-weight support system and pausing to prevent falls.

Since this proof-of-concept study involved a single patient, Do said, further research is needed to establish whether the results can be duplicated in a larger population of individuals with paraplegia.

“Once we’ve confirmed the usability of this noninvasive system, we can look into invasive means, such as brain implants,” said Do, an assistant clinical professor of neurology. “We hope that an implant could achieve an even greater level of prosthesis control because brain waves are recorded with higher quality. In addition, such an implant could deliver sensation back to the brain, enabling the user to feel his legs.”

Christine King, Po Wang, Colin McCrimmon and Cathy Chou of UCI contributed to the study, which received support from the National Science Foundation (grant 1160200).

-- Tom Vasich / UCI

OUTSTANDING STUDENT HIGHLIGHTS

Two Grad Students Earn IGERT Fellowships

Congratulations to Sara Sameni and Andrew Trinh on being selected for the 2015 Biophotonics across Energy, Space and Time, (BEST) Interdisciplinary Graduate Education and Research Traineeship (IGERT) program at the Beckman Laser Institute. The program is intended to attract trainees with a diverse set of academic backgrounds across the biomedical sciences, physical sciences and engineering who share a passion to develop and utilize new photonic methods to measure, image, probe and manipulate biological components, processes and systems.

BME Students Shine at Local Grad Slam

Three out of the eight UCI Grad Slam finalists this year were BME students: Jessica Hsieh, Xiang Li and Elena Liang. The competition, held earlier this month at the UC Irvine Newkirk Alumni Center, is part of a wider UC contest to showcase the best three-minute research presentations by graduate scholars systemwide. Hsieh won third place and $250. The third-year doctoral student, who works in the lab of biomedical engineering professor Wendy Liu, says she enjoyed competing. “I had a great time doing Grad Slam because I really like the challenge of communicating my research using non-scientific terms,” says Hsieh. “I would definitely compete again next year.”

Two Receive ICTS Predoctoral Fellowship Awards

Ben LertsakdadetGraduate student Ben Lertsakdadet has been awarded a one-year predoctoral fellowship from the Institute for Clinical and Translational Science (ICTS) for “Noninvasive, Point-of-Care Monitoring of Neonatal Intestinal Blood Flow.” Lertsakdadet works in the lab of Associate Professor Bernard Choi and collaborates with Dr. Mustafa Kabeer, a surgeon with a pediatric and critical care specialty at the Children’s Hospital of Orange County (CHOC).

Robert Warren Graduate student Robert Warren has been awarded a one-year predoctoral fellowship from the ICTS for “Development of Non-invasive, Functional, Optical Imaging for Monitoring and Detecting Cardiovascular Disease.” Warren works in the Diffuse Optical Spectroscopy & Imaging Lab under the supervision of Professor Bruce Tromberg and with Dr. Shaista Malik, assistant professor of cardiology and program director of the Cardiovascular Disease Fellowship, Division of Cardiology in UCI’s Department of Medicine.

FACULTY AND POSTDOC ACCOLADES

AHA Postdoctoral Fellowship Awarded to Hamed Alavi

The American Heart Association (AHA) has awarded a two-year Postdoctoral Fellowship to Hamed Alavi to support his project on a hybrid tissue-engineered heart valve. Alavi, a biomedical engineering postdoctoral researcher in Professor Arash Kheradvar’s lab, has been working for about six years on a new valve that aims to combine patients' own cells with a metal alloy mesh, providing a potentially self-regenerative function with better durability. The AHA funding allows Alavi to move forward with analyzing the valves’ function and biocompatibility in a series of animal studies. “We believe this new hybrid technology will significantly improve a patient’s quality of life by eliminating the need for lifelong medications without compromising the durability of the valve,” said Alavi. “This is particularly beneficial for younger patients who are in need of a heart valve replacement.”

Bernard Choi Elected SPIE Fellow

Associate Professor Bernard Choi was elected a Fellow of the International Society of Optics and Photonics (SPIE) for achievements in biophotonics and biomedical optics of skin and microvascular therapy. His election was announced at the annual SPIE Photonics West meeting held in San Francisco, Calif., February 13-18, 2016; 32 new SPIE Fellows were elected this year. They were honored for technical achievement and service to the general optics community and SPIE in particular. More than 1,000 SPIE members have become Fellows since the Society’s inception in 1955.

AHA Grants Innovation Research Award to Arash Kheradvar

Associate Professor Arash Kheradvar has received an Innovative Research Grant from the American Heart Association (AHA). The grant will support his efforts to improve outcomes in heart valve replacement for patients with severe aortic valve stenosis -- a narrowing of the valve, which limits blood flow from the heart to the body. The two-year $150,000 grant will help fund the development and testing of an ultrasound-guided delivery system for transcatheter heart valve replacement (TAVR). TAVR is a fairly new, less invasive treatment option for patients who cannot tolerate open heart surgery. Recently approved in the U.S., the procedure allows the replacement valve to be inserted in a thin flexible tube and delivered to the heart through the femoral artery in the groin.

The AHA Innovative Research Grants support high-risk, high-reward projects that could ultimately lead to critical discoveries or major advancements that accelerate the field of cardiovascular and stroke research.

Chang Liu Named a Sloan Research Fellow

Assistant Professor Chang Liu has been awarded a 2016 Sloan Research Fellowship for his pioneering efforts to engineer synthetic genetic systems, which can be used to advance the discovery and production of cancer drugs and useful enzymes. Bestowed annually since 1955 by the Alfred P. Sloan Foundation, the two-year fellowships are granted to 126 early-career scientists and scholars in the U.S. and Canada whose achievements and potential identify them as the next generation of scientific leaders. Fellows — who are nominated by their peers — receive $55,000 to further their work.

“DNA replication is the most central process of life, and we’ve developed a way to re-engineer it inside living cells,” said Liu. “We’re very excited about the possibilities. Not only will this let us rapidly evolve therapeutic biomolecules, it acts as a platform for building genetic systems from the ground up.”

Zoran Nenadic Wins Young Researchers Award

Associate Professor Zoran Nenadic was honored with the Hiruma-Wagner Award for young researchers from the Japanese Research Foundation on Feb. 25, 2016, for his work on "Brain-Computer Interface for Restoration of Overground Walking after Paraplegia."

The Conference of Peace through Mind/Brain Science is a biannual, invitation-only meeting that brings together 30 to 40 scientists worldwide. It was started in 1988 by Teruo Hiruma of Hamamatsu Photonics K.K. and Henry N. Wagner Jr., of Johns Hopkins University in an effort to bring together scientists from Japan, the U.S. and the Soviet Union in order to foster scientific connections during the Cold War era. The conference is sponsored by Hamamatsu Photonics K.K.-- a world leader in the development and production of optical devices and technologies.

NIH Awards Grant to Zhongping Chen

Professor Zhongping Chen has been awarded a four-year grant from the National Eye Institute, National Institutes of Health (NIH), in support of his project “High Resolution Elastography of Retina under Prosthetic Electrical Stimulation.” With this research, he hopes to develop and characterize novel tools for imaging the elastic properties of the retina under prosthetic electrical stimulation, a treatment used for individuals with photoreceptor degenerative diseases including retinitis pigmentosa. The imaging technique will generate images depicting local displacements with nanometer resolution, providing details about the elastic properties of the retina that cannot be obtained with current imaging methods.

NIH/NHLBI Grants Support to Anna Grosberg

Professor Anna Grosberg’s work on cardiac functional and structural implications of lamin A/C mutations has been awarded a Natural Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) grant. The five-year award will support her lab’s research to correlate functional and structural properties to genetic variations of cardiomyocytes specific to patients who have genetic mutations known to lead to heart disease. The outcome could advance understanding of structural and functional underpinnings of diseases such as cardiomyopathies and identification of genes.

Bruce Tromberg Elected OSA Fellow

BME faculty member and Beckman Laser Institute Director Bruce Tromberg has been elected a Fellow of the Optical Society (OSA), a nearly 100-year-old international association of optics and photonics scientists, engineers and business leaders. Tromberg is one of 77 newly elected 2016 Fellows and was recognized for “serving as an advocate for and a leader of the biophotonics community as well as for pioneering the development and clinical application of spatially and temporally modulated light imaging.” Only 10 percent of the organization’s total membership is honored with this fellowship, which is based on members’ contributions to the field, optics-related publications and patents, leadership and service.

Two Faculty Win Seed Funding and Technology Development Funds

Two BME researchers — Bernard Choi and Abe Lee — have won awards from the Research Seed Funding Program and the Technology Development Innovation Fund, a new collaboration of the offices of the UCI provost, vice chancellor for research, vice chancellor for health affairs and the university’s Applied Innovation center. Competition was fierce; 141 proposals were submitted across three categories, and 19 projects were funded. Six Samueli School-affiliated researchers received awards, including the two BME faculty. Abe Lee, biomedical engineering chair and William J. Link Professor, won $25,000 for an integrated microfluidic system for sample enrichment and concentration. Bernard Choi, biomedical engineering associate professor, won $33,700 for intraoperative blood-flow imaging during pediatric intestinal surgery.

FOCUS ON RESEARCH

Chemical changes in brain cells caused by disturbances in the body’s day-night cycle may be a key underlying cause of the learning and memory loss associated with Alzheimer’s disease, according to a UC Irvine study.

The research on mice, led by UCI biomedical engineering professor Gregory Brewer, provides the first evidence that circadian rhythm-altering sleep disruptions similar to jet lag promote memory problems and chemical alterations in the brain.

People with Alzheimer’s often have problems with sleeping or may experience changes in their slumber schedule. Scientists do not completely understand why these disturbances occur.

“The issue is whether poor sleep accelerates the development of Alzheimer’s disease or vice versa,” said Brewer, who’s affiliated with UCI’s Institute for Memory Impairments and Neurological Disorders. “It’s a chicken-or-egg dilemma, but our research points to disruption of sleep as the accelerator of memory loss.”

In order to examine the link between learning and memory and circadian disturbances, his team altered normal light-dark patterns with an eight-hour shortening of the dark period every three days for young mouse models of Alzheimer’s disease and normal mice.

The resulting jet lag greatly reduced activity in both sets of mice, and the researchers found that in water maze tests, the AD mouse models had significant learning impairments absent in the AD mouse models not exposed to light-dark variations and in normal mice with jet lag.

In follow-up tissue studies, they saw that jet lag caused a decrease in glutathione levels in the brain cells of all the mice. But these levels were much lower in the AD mouse models and corresponded to poor performance in the water maze tests. Glutathione is a major antioxidant that helps prevent damage to essential cellular components.

Glutathione deficiencies produce redox changes in brain cells. Redox reactions involve the transfer of electrons, which leads to alterations in the oxidation state of atoms and may affect brain metabolism and inflammation.

Brewer pointed to the accelerated oxidative stress as a vital component in Alzheimer’s-related learning and memory loss and noted that potential drug treatments could target these changes in redox reactions.

“This study suggests that clinicians and caregivers should add good sleep habits to regular exercise and a healthy diet to maximize good memory,” he said.

Kelsey LeVault and Shelley Tischkau of the Southern Illinois University School of Medicine contributed to the research, which received support from the National Institutes of Health (grant R01 AG032431).

-- Tom Vasich / UCI

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